Particle air pollution has been associated with cardiovascular hospitalization and mortality in population-based studies throughout the world. The program project goal is to understand the relation of particle pollution to clinical, physiologic and biochemical endpoints reflecting potential mechanisms underlying these associations. The investigators have focused on endpoints influenced by autonomic regulation, and have found pollution effects on heart rate variability and on ventricular and supraventricular tachyarrhythmias. The investigators also have published or preliminary evidence for associations of particle pollution with elevated pulmonary/systemic inflammatory markers (e.g. exhaled nitric oxide (NO), intercellular adhesion molecule (ICAM-1), oxygen desaturation, ST-segment repression, elevated blood pressure, and, most recently, reduced vascular reactivity. Building on these observations, the principal investigators propose to broaden their focus to evaluate not only autonomic mechanisms, but also potentially interrelated vascular and inflammatory mechanisms for air pollution cardiovascular effects in humans. This evaluation requires a multidisciplinary approach joining experts in epidemiology, air pollution measurement, cardiology and electrophysiology;diabetes and measurement of vascular and inflammatory outcomes, and environmental statistics. Projects proposed would provide data on a spectrum of at-risk subjects including the elderly, and populations with Type 2 diabetes, coronary artery disease, implanted cardioverter defibrillators, and acute cerebrovascular events. Primary outcomes of interest will include brachial artery diameter and endothelium-dependent flow-mediated dilation, heart rate variability, tachyarrhythmias in patients with implanted defibrillators, and acute ischemic cerebrovascular events. Markers of pulmonary and systemic inflammation and endothelial dysfunction will be evaluated as intermediate outcomes. The investigators will also differentiate effects of particle components closely associated with traffic (e.g., black carbon) and long-range transport (e.g., sulfate), with improved assessment of spatial as well as temporal differences in exposure. To carry out the proposed projects, several core services will be required. These will include the following: an Administrative Core;a Data Coordination and Statistics Core to apply consistent methodology to gathering, processing, checking and analysis of data;the Particle Exposure Characterization Core to provide detailed characterization and quantification of ambient pollution;and the Health Outcomes Core to provide vascular, electrophysiologic, and endocrine assessment and measures of inflammation/endothelial dysfunction. These studies will provide additional insight into the relative sensitivity of different subgroups to air pollution, and potential mechanisms whereby ambient pollution is associated with excess morbidity and mortality. Moreover, the study may provide clues as to how to develop preventive strategies to reduce this excess.